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Invest Ophthalmol Vis Sci. 2020 Mar 9;61(3):13. doi: 10.1167/iovs.61.3.13.
To investigate the efficacy of intravitreal administration of resveratrol (RSV) in a microbead-induced high intraocular pressure (IOP) murine model for glaucoma.
Experiments were performed using adult C57BL/6JJcl mice. Polystyrene microbeads were injected into the anterior chamber to induce IOP elevation. Retinal flat-mounts and sections were assessed by immunohistochemistry to detect the expression of reactive oxygen species and acetyl-p53 in retinal ganglion cells (RGCs), brain-derived neurotrophic factor (BDNF) in Müller glial cells (MGCs), and the receptor tropomyosin receptor kinase B (TrkB) in RGCs. Light cycler real-time PCR was also used for confirming gene expression of BDNF in primary cultured MGCs exposed to RSV.
Microbeads induced high IOP followed by RGC death and axon loss. Administration of RSV rescued RGCs via decreased reactive oxygen species generation and acetyl-p53 expression in RGCs and upregulated BDNF in MGCs and TrkB expression in RGCs, which exhibited a strong cytoprotective action against cell death through multiple pathways under high IOP.
Our data suggest that administration of RSV may delay the progress of visual dysfunction during glaucoma and may therefore have therapeutic potential.
研究白藜芦醇(RSV)在微珠诱导的青光眼高眼压(IOP)小鼠模型中的疗效。
使用成年 C57BL/6JJcl 小鼠进行实验。将聚苯乙烯微珠注射到前房以诱导 IOP 升高。通过免疫组织化学检测视网膜神经节细胞(RGCs)中活性氧和乙酰化 p53 的表达、Müller 胶质细胞(MGCs)中的脑源性神经营养因子(BDNF)以及 RGCs 中的原肌球蛋白受体激酶 B(TrkB)的表达,评估视网膜扁平装片和切片。还使用实时荧光定量 PCR 确认 RSV 处理的原代培养 MGCs 中 BDNF 的基因表达。
微珠诱导高 IOP 后,RGC 死亡和轴突丢失。RSV 给药通过减少 RGC 中的活性氧生成和乙酰化 p53 表达,并上调 MGC 中的 BDNF 和 RGC 中的 TrkB 表达,从而挽救了 RGCs,对高 IOP 下的细胞死亡具有强烈的细胞保护作用,通过多种途径。
我们的数据表明,RSV 的给药可能会延迟青光眼期间视觉功能障碍的进展,因此可能具有治疗潜力。